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Raptor mediates the selective inhibitory effect of cardamonin on RRAGC-mutant B cell lymphoma

Ying Liu1, Yanting Zhu1, Huajiao Chen1

  • 1Department of Pharmacy, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University Fujian Maternity and Child Health Hospital, 18 Daoshan Road, Fuzhou, 350001, Fujian, China.

BMC Complementary Medicine and Therapies
|September 25, 2023
PubMed
Abstract

Insights

Cardamonin selectively targets lymphoma cells with specific RRAGC mutations by disrupting mTORC1 signaling. This natural compound offers a promising, individualized therapy for follicular lymphoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Mechanistic target of rapamycin complex 1 (mTORC1) is implicated in lymphoma progression.
  • Oncogenic RRAGC mutations in follicular lymphoma enhance mTORC1 activation via Raptor interaction, promoting lymphomagenesis.
  • Cardamonin is known to inhibit mTORC1 by reducing Raptor protein levels.

Purpose of the Study:

  • To investigate the inhibitory effects of cardamonin on RRAGC-mutant lymphoma.
  • To elucidate the mechanism of action of cardamonin in this context.
  • To assess cardamonin as a potential targeted therapy for RRAGC-mutant lymphoma.

Main Methods:

  • Cell viability assessed via CCK-8 assay.
  • Protein expression and phosphorylation analyzed by western blotting.
  • mTOR, Raptor, and RagC interactions studied using co-immunoprecipitation.
  • RagC wild-type (RagCWT) and mutant (RagCT90N) cell lines generated.
  • Raptor knockdown performed using shRNA.
  • In vivo anti-tumour efficacy evaluated in a xenograft model.

Main Results:

  • Cardamonin disrupted mTOR complex interactions by decreasing Raptor protein levels.
  • Overexpression of RagCT90N increased cell proliferation and mTORC1 activation.
  • RagCT90N-mutant cells showed increased sensitivity to cardamonin compared to normal and RagCWT cells.
  • Cardamonin more effectively inhibited mTOR and p70 S6 kinase 1 phosphorylation in RagCT90N-mutant cells.
  • Raptor knockdown abrogated cardamonin's inhibitory effects.
  • In vivo studies confirmed higher sensitivity of RagCT90N-mutant tumors to cardamonin.

Conclusions:

  • Cardamonin demonstrates selective therapeutic efficacy against RagCT90N-mutant lymphoma cells.
  • Cardamonin holds potential as an individualized therapeutic agent for follicular lymphoma harboring RRAGC mutations.
Keywords:
CardamoninFollicular lymphomaRagCRaptormTORC1

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